Mutational Signatures Are Critical for Proper Estimation of Purifying Selection Pressures in Cancer Somatic Mutation Data When Using the dN/dS Metric.

ABSTRACT: Large cancer genome sequencing initiatives have led to the identification of cancer driver genes based on signals of positive selection in somatic mutation data. Additionally, the identification of purifying (negative) selection has the potential to identify essential genes that may be of therapeutic interest. The most widely used way of quantifying selection pressures in protein-coding genes is the dN/dS metric, which compares non-synonymous to synonymous substitution rates. In this study, we examine whether and how this metric is influenced by the mutational processes that have been active during tumor evolution. We use exome sequencing data from six different cancer types from The Cancer Genome Atlas (TCGA) and demonstrate that dN/dS in its basic form, where uniform base substitution pr

SUBMITTER: Van den Eynden J 

PROVIDER: S-EPMC5462936 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature